scholarly journals Protective Effect of SIRT1 Activator on the Knee With Osteoarthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhenquan Zhou ◽  
Zhenhan Deng ◽  
Yuwei Liu ◽  
Yizi Zheng ◽  
Shiwei Yang ◽  
...  

Osteoarthritis (OA), one of the most common chronic musculoskeletal disorders, is deemed to be correlated with aging. The SIRT1 activator, resveratrol, acts as a crucial regulator of aging and may have a potential therapeutic effect on OA. Rabbit OA models were established through destabilized medial meniscus surgery. A total of 40 healthy male New Zealand rabbits were divided into five groups: control group (sham operation), OA group, as well as low dose (LD), middle dose (MD), and high dose (HD) resveratrol-treated OA groups. 6 weeks after operation, 0.8 ml of normal saline was injected into the knee joints every other day in the control and OA groups, and 0.8 ml of 5, 10, and 15 μmol/L resveratrol was injected into the knee joints every other day in the LD, MD, and HD group, respectively. The rabbits were sacrificed 2 weeks after medication, and the articular cartilage of the knee joint was collected for Micro-CT, histology and Western blot analysis. Obvious articular cartilage lesion and joint space narrowing were detected in the OA group. Compared with the OA group, less osteoarthritic changes were observed in the MD and HD groups. The MD and HD groups had significantly lower bone volume fraction, trabecular number and Mankin scores than the LD and OA groups (p < 0.05). No significant difference was found between the OA and LD groups (p > 0.05). The expressions of SIRT1 and p53 detected by western blot were consistent with the aforementioned findings. Therefore, resveratrol can activate the SIRT1 gene to play a protective role in the OA process by inhibiting chondrocyte apoptosis, trabecular bone number increasing of the subchondral bone, as well as elevation of bone density. It demonstrated the importance of SIRT1 in maintaining articular cartilage health and provided a promising therapeutic intervention in the treatment of OA.

Author(s):  
Qinglin Meng ◽  
Mengqi Liu ◽  
Weiwei Deng ◽  
Ke Chen ◽  
Botao Wang ◽  
...  

Background: Calcium-suppressed (CaSupp) technique involving spectral-based images has been used to observe bone marrow edema by removing calcium components from the image. Objective: This study aimed to evaluate the knee articular cartilage using the CaSupp technique in dual-layer detector computed tomography (DLCT). Methods: Twenty-eight healthy participants and two patients with osteoarthritis were enrolled, who underwent DLCT and magnetic resonance imaging (MRI) examination. CaSupp images were reconstructed from spectral-based images using a calcium suppression algorithm and were overlaid conventional CT images for visual evaluation. The morphology of the knee cartilage was evaluated, and the thickness of the articular cartilage was measured on sagittal proton density– weighted and CaSupp images in the patellofemoral compartment. Results: No abnormal signal or density, cartilage defect, and subjacent bone ulceration were observed in the lateral and medial femorotibial compartments and the patellofemoral compartment on MRI images and CaSupp images for the 48 normal knee joints. CaSupp images could clearly identify cartilage thinning, defect, subjacent bone marrow edema, and edema of the infrapatellar fat pad in the same way as MRI images in the three knee joints with osteoarthritis. A significant difference was found in the mean thickness of the patellar cartilage between MRI images and CaSupp images, while the femoral cartilage presented no significant difference in thickness between MRI images and CaSupp images over all 48 knee joints. Conclusion: The present study demonstrated that CaSupp images could effectively be used to perform the visual and quantitative assessment of knee cartilage.


2021 ◽  
pp. 096452842110207
Author(s):  
Alexa P Spittler ◽  
Maryam F Afzali ◽  
Richard B Martinez ◽  
Lauren A Culver ◽  
Sarah E Leavell ◽  
...  

Objective: Faced with the frustration of chronic discomfort and restricted mobility due to osteoarthritis (OA), many individuals have turned to acupuncture for relief. However, the efficacy of acupuncture for OA is uncertain, as much of the evidence is inconclusive. The purpose of this study was to evaluate electroacupuncture (EA) in a rodent model of OA such that conclusions regarding its effectiveness for symptom or disease modification could be drawn. Methods: Ten 12-month-old male Hartley guinea pigs—which characteristically have moderate to advanced OA at this age—were randomly assigned to receive EA for knee OA (n = 5) or anesthesia only (control group, n = 5). Treatments were performed three times weekly for 3 weeks, followed by euthanasia 2 weeks later. Gait analysis and enclosure monitoring were performed weekly to evaluate changes in movement. Serum was collected for inflammatory biomarker testing. Knee joints were collected for histology and gene expression. Results: Animals receiving EA had significantly greater changes in movement parameters compared to those receiving anesthesia only. There was a tendency toward decreased serum protein concentrations of complement component 3 (C3) in the EA group compared to the control group. Structural and antioxidant gene transcripts in articular cartilage were increased by EA. There was no significant difference in total joint histology scores between groups. Conclusion: This study provides evidence that EA has a positive effect on symptom, but not disease, modification in a rodent model of OA. Further investigations into mechanistic pathways that may explain the efficacy of EA in this animal model are needed.


Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.


2007 ◽  
Vol 7 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Sabaheta Hasić ◽  
Radivoj Jadrić ◽  
Emina Kiseljaković ◽  
Zakira Mornjaković ◽  
Mira Winterhalter-Jadrić

In our investigation, we used short-time model of myocardial infarction of rats induced by high dose of isoproterenol (ISP). We investigated cardiac troponin T blood level (cTnT) and histological characteristics of rat myocardium. ISP, single, intraperitoneal dose 250 mg/kg was given to male, adult, Wistar rats (n=12). Rats were distributed depending on their body weight in subgroups: ISP I (BW 260-280g) and ISP II (BW 250-400g). Control group (n=9) was treated with intraperitoneal dose of 0,95% NaCl. Cardiac TnT was measured by electrochemiluminiscence (ECLA) sandwich immunoassay in rat serum 4 hours after ISP application. Rats’ hearts were dissected and examined by qualitative histological method (HE). Statistical significance was set at 0,05. There was significant difference in cTnT of ISP II (p=0,0001) vs. control and ISP I (p<0,05) vs. control. Significant difference was beetween ISP I and ISP II subgroups (p<0.001). The accent of histological changes of myocardium was on nuclei of cell. Cells showed acydophilic changes and nuclei disappearance as signs of coagulative necrosis development. Extensivity of histological changes were different beetween ISP I and ISP II subgroup. Used dose of ISP induced development of myocardial necrosis in rats. Suben-docardial portion of myocardium was more vulnerability than subepicardial portion. Rats of ISP II had more extensive histological changes than these in ISP I. Administered doses of ISP enabled cTnT utilization as a marker of myocardial necrosis.


Author(s):  
Hairuo Lin ◽  
Yingqi Zhu ◽  
Cankun Zheng ◽  
Donghong Hu ◽  
Siyuan Ma ◽  
...  

Background: Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5-6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. Methods: C57BL/6 mice were submitted to 21 days of swimming training to develop PMH. After termination of exercise, PMH regressed within 1 week. PMH regression mice (exercise hypertrophic preconditioning group, EHP) and sedentary mice (control group) then underwent transverse aortic constriction (TAC) or a sham operation for 4 weeks. Cardiac remodeling and function were evaluated using echocardiography, invasive left ventricular hemodynamic measurement and histological analysis. LncRNA sequencing, chromatin immunoprecipitation assay (ChIP), and comprehensive identification of RNA-binding proteins by mass spectrometry (CHIRP-MS) and Western blot were used to investigate the role of Mhrt779 involved in the anti-hypertrophy effect induced by EHP. Results: At 1 and 4 weeks after TAC, the EHP group showed less increase in myocardial hypertrophy and lower expression of the Nppa and Myh7 genes than the sedentary group. At 4 weeks after TAC, EHP mice had less pulmonary congestion, smaller left ventricular dimensions and end-diastolic pressure, and a larger left ventricular ejection fraction and maximum pressure change rate than sedentary mice. Quantitative polymerase chain reaction (qPCR) revealed that the long noncoding myosin heavy chain associated RNA transcript Mhrt779 was one of the markedly upregulated long noncoding RNAs in the EHP group. Silencing of Mhrt779 attenuated the antihypertrophic effect of EHP in mice with TAC and in cultured cardiomyocytes treated with angiotensin II, and overexpression enhanced the antihypertrophic effect. By ChIP and qPCR, we found that EHP increased histone 3 trimethylation (H3K4me3 and H3K36me3) at the a4 promoter of Mhrt779 . CHIRP-MS and Western blot showed that Mhrt779 can bind Brg1 to inhibit the activation of Hdac2/Akt/GSK3β pathway induced by pressure overload. Conclusions: Myocardial hypertrophy preconditioning evoked by exercise increases resistance to pathological stress via an antihypertrophic effect mediated by a signal pathway of Mhrt779 /Brg1/Hdac2/p-Akt/p-GSK3β.


2020 ◽  
Author(s):  
Melina Bellini ◽  
Michael Andrew Pest ◽  
Manuela Miranda Rodrigues ◽  
Ling Qin ◽  
Jae-Wook Jeong ◽  
...  

Abstract Background: Osteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the Epidermal Growth Factor Receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of articular cartilage and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study. Methods: Utilizing knee joints from cartilage-specific Mig-6 overexpressing (Mig-6over/over) mice (at multiple time points), we evaluated the articular cartilage using histology, immunohistochemical staining and semi-quantitative histopathological scoring (OARSI) at multiple ages. MicroCT analysis was employed to examine skeletal morphometry, body composition, and bone mineral density.Results: Our data show that cartilage-specific Mig-6 overexpression did not cause any major developmental abnormalities in articular cartilage, although Mig-6over/over mice have slightly shorter long bones compared to the control group. Moreover, there was no significant difference in bone mineral density and body composition in any of the groups. However, our results indicate that Mig-6over/over male mice show accelerated cartilage degeneration at 12 and 18 months of age. Immunohistochemistry for SOX9 demonstrated that the number of positively stained cells in Mig-6over/over mice was decreased relative to controls. Immunostaining for MMP13 appeared increased in areas of cartilage degeneration in Mig-6over/over mice. Moreover, staining for phospho-EGFR (Tyr-1173) and lubricin (PRG4) was decreased in the articular cartilage of Mig-6over/over mice. Conclusion: Overexpression of Mig-6 in articular cartilage causes no major developmental phenotype; however, these mice develop earlier OA during aging. These data demonstrate that Mig-6/EGFR pathways is critical for joint homeostasis and might present a promising therapeutic target for OA.


2018 ◽  
Vol 52 (4) ◽  
pp. 185-191
Author(s):  
Tomomi Nobashi ◽  
Tsuneo Saga ◽  
Yuji Nakamoto ◽  
Yoichi Shimizu ◽  
Sho Koyasu ◽  
...  

AbstractObjective. This study investigated whether the metformin (Met)-induced enhanced intestinal uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is reduced by loperamide, a long-acting anti-diarrheal agent. Methods. Mean18F-FDG uptake in the mouse small intestine and colon with Met exposure was compared with that in control mice. In the Met group, high-dose (1.0 mg/kg body weight) and low-dose (0.1 mg/kg body weight) loperamide were introduced, and18F-FDG uptake in the small intestine and colon was compared with that of control mice administered high-dose loperamide. The percent injected dose of18F-FDG per gram of tissue (%ID/g) in the extracted tissues was then determined. Results.18F-FDG uptake increased significantly in the small intestine (0.64±0.06 vs. 1.01±0.15, p=0.040) and, especially, the colon (0.46±0.13 vs. 2.16±0.51, p<0.001) after Met exposure. Neither high-dose nor low-dose loperamide significantly reduced18F-FDG uptake in the small intestine (0.82±0.31 vs. 0.84±0.22, p=0.93 and 0.78±0.25 vs. 0.70±0.15, p=0.13, respectively) or colon (2.13±0.41 vs. 1.67±0.55, p=0.063 and 1.77±0.39 vs. 1.80±0.25, p=0.56, respectively). The colonic %ID/g was significantly higher in Met groups irrespective of loperamide introduction than in control group, whereas the significant difference in the small intestine was observed only between Met and control groups. Conclusion. Metformin increased18F-FDG uptake in intestines especially in colon. Loperamide administration partially, but not sufficiently, suppresses the Met-induced increased colonic uptake of18F-FDG.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Huacheng Hou ◽  
Ke Zheng ◽  
Guanghu Wang ◽  
Shiro Ikegawa ◽  
Minghao Zheng ◽  
...  

Autologous osteochondral transplantation (AOT) is a method for articular cartilage repair. However, several disadvantages of this method have been reported, such as transplanted cartilage degeneration and the lack of a connection between the grafted and adjacent cartilage tissues. To evaluate the effect of intra-articular administration of trichostatin A (TSA) on AOT, we conducted a case control study in a rabbit model. International Cartilage Repair Society (ICRS) macroscopic scores, the modified O’Driscoll histology scores, and real-time PCR were utilized to evaluate the results. At 4 weeks, both macroscopic and histological assessments showed that there was no significant difference between the TSA and control groups. However, the mean macroscopic and histological scores for the TSA-treated group were significantly higher than the scores for the control group at 12 weeks. TSA was shown to directly reduce collagen type II (COL2), aggrecan, matrix metalloproteinase (MMP), and a disintegrin and metalloproteinase domain with thrombospondin motifs 5 (ADAMTS-5) expression and to simultaneously repress the upregulation of MMP-3, MMP-9, and MMP-13 levels induced by interleukin 1β(IL-1β) in chondrocytes. In conclusion, TSA protects AOT grafts from degeneration, which may provide a benefit in the repair of articular cartilage injury.


2018 ◽  
Vol 7 (4.26) ◽  
pp. 136
Author(s):  
Irfiansyah Irwadi ◽  
Hayuris Kinandita ◽  
Jamaluddin Mahmud ◽  
Lilik Herawati

Aim: Antioxidants, such as vitamin C and vitamin E, is widely used as supplements. The aim of this study is to analyze the profile of blood glucose, serum insulin, and  HOMA in active teenagers after vitamin C and vitamin E supplementation.Methods: Subjects (14-16 y.o) consisted of 12 boys and 5 girls, divided into 3 groups: control (4 boys, 2 girls), ‘moderate dose’ of vitamin C and vitamin E combination group (5 boys, 1 girls), and ‘high dose’ of vitamin C and vitamin E combination group (3 boys, 2 girls). The treatment was given for 5 days. Vitamin C and vitamin E for ‘moderate dose’ was 500mg;  200IU, and for ‘high dose’ was 1000mg; 400IU. Fasting Blood Glucose (FGB) and 1 hour BG (1hr_BG), fasting serum insulin (FSI) and 1 hour SI (1hr_SI) was collected after treatment. We also calculated the HOMA-IR and HOMA-β.Result: There was no significant difference on FBG, 1hr_BG, FSI, 1hr_SI, HOMA-IR, and HOMA-β (p≥ 0.05). However, mean FBG and 1hr_BG tended to be higher on the treatment groups. The control group had the lowest HOMA-IR and the highest HOMA-β.Conclusions: We suggest that the supplementation of vitamin C and vitamin E in active teenagers is not essential on glucose homeostasis.  


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Qing Wang ◽  
Xia Guo ◽  
Mu-Qing Liu ◽  
Xiao-Yun Wang ◽  
Yong-Ping Zheng

To investigate the effect of laser acupuncture (LA) on disuse changes in articular cartilage using ultrasound biomicroscopy (UBM), Eighteen rats were randomly divided into the control group (C), the tail-suspended group (T), and the tail-suspended with LA treatment group (L). During 28-day suspension period, group L were treated with LA at acupoints on the left hindlimb while group T had a sham treatment. Ultrasound roughness index (URI), integrated reflection coefficient (IRC), integrated backscatter coefficient (IBC), cartilage thickness, and ultrasonographic score (US) of articular cartilage at patella were measured by using an ultrasound biomicroscopy system (UBS). Compared with the group C, URI significantly (P<0.01) increased by 60.9% in group T, increased by 38.1% in group L. In addition, unloading induced a significant cartilage thinning (P<0.05) in group T, whereas cartilage thickness in group L was140.22±19.61 μm reaching the level of the control group (147.00±23.99 μm). There was no significant difference in IRC, IBC, and US among the three groups. LA therapy could help to retain the quality of articular cartilage which was subjected to unloading. LA would be a simple and safe nonpharmacological countermeasure for unloading-induced osteoarthritis. The UBM system has potential to be a sensitive, specific tool for quantitative assessment of articular cartilage.


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